Radiologic and Clinical Outcomes of the Dovetailed Notch Scarf Osteotomy for Correcting the First Metatarsal Pronation in Moderate to Severe Hallux Valgus Deformity: A Comparative Study.

BACKGROUND: The traditional scarf osteotomy (TSO) has limited ability to correct the first metatarsal pronation. A novel modification that we refer to as a "dovetailed notch scarf osteotomy" (DNSO) has been developed to enhance the ability to correct coronal plane pronation. The study aimed to observe and compare TSO to DNSO in the treatment of moderate to severe hallux valgus deformity. METHODS: This retrospective study included 78 feet that had a TSO and 105 feet that had a DNSO. Minimum follow-up was 24 months. Weightbearing computed tomography (WBCT) and weightbearing anterior-posterior (AP) radiographs were taken preoperatively and at the last follow-up. We measured the intermetatarsal angle (IMA), hallux valgus angle, distal metatarsal articular surface angle on AP radiographs and first metatarsal coronal pronation angle (α angle), tibial sesamoid coronal grading, and first metatarsal length on WBCT. Clinical assessment was done using visual analog scale (VAS), American Orthopaedic Foot & Ankle Society (AOFAS) ankle-hindfoot scale, Foot and Ankle Ability Measure (FAAM), and the 36-Item Short Form Health Survey (SF-36). The occurrence of postoperative complications was also documented. RESULTS: The DNSO group exhibited a significantly higher correction amount of α angle and IMA (14.3 ± 9.9 and 10.3 ± 4.6 degrees) than the TSO group (8.6 ± 5.9 and 5.4 ± 5.9 degrees) during the final follow-up assessment (P < .05).The DNSO group (10.1 [8.0-12.0] degrees and 4.8 [3.9-5.6] degrees) demonstrated significantly smaller α angle and IMA compared with the TSO group (4.8 [3.9-5.6] degrees and 9.5 [7.5-11.5] degrees) at 24 months postsurgery (P < .05). The postoperative FAAM activities of daily living and SF-36 physical functioning scores were significantly higher in the DNSO group (97.2 ± 3.3 and 95.7 ± 4.4 points) compared with the TSO group (92.3 ± 3.3 and 87.7 ± 8.7 points) (P < .05). Additionally, hallux varus occurred in 1 case in the DNSO group, whereas 4 cases were observed in the TSO group. CONCLUSION: Two osteotomy methods can effectively correct moderate to severe hallux valgus deformity. Compared with the TSO, the DNSO has stronger correction ability. The most crucial aspect lies in its controllability when correcting first metatarsal pronation and addressing IMA. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

Plant-Derived Exosome-Like Nanoparticles: Emerging Nanosystems for Enhanced Tissue Engineering.

Tissue engineering holds great potential for tissue repair and rejuvenation. Plant-derived exosome-like nanoparticles (ELNs) have recently emerged as a promising avenue in tissue engineering. However, there is an urgent need to understand how plant ELNs can be therapeutically applied in clinical disease management, especially for tissue regeneration. In this review, we comprehensively examine the properties, characteristics, and isolation techniques of plant ELNs. We also discuss their impact on the immune system, compatibility with the human body, and their role in tissue regeneration. To ensure the suitability of plant ELNs for tissue engineering, we explore various engineering and modification strategies. Additionally, we provide insights into the progress of commercialization and industrial perspectives on plant ELNs. This review aims to highlight the potential of plant ELNs in regenerative medicine by exploring the current research landscape and key findings.

Enhancing angiogenesis: Innovative drug delivery systems to facilitate diabetic wound healing.

Diabetic wounds (DW) constitute a substantial burden on global healthcare owing to their widespread occurrence as a complication of diabetes. Angiogenesis, a crucial process, plays a pivotal role in tissue recovery by supplying essential oxygen and nutrients to the injury site. Unfortunately, in diabetes mellitus, various factors disrupt angiogenesis, hindering wound healing. While biomaterials designed to enhance angiogenesis hold promise for the treatment of DWs, there is an urgent need for more in-depth investigations to fully unlock their potential in clinical management. In this review, we explore the intricate mechanisms of angiogenesis that are crucial for DW recovery. We introduce a rational design for angiogenesis-enhancing drug delivery systems (DDS) and provide a comprehensive summary and discussion of diverse biomaterials that enhance angiogenesis for facilitating DW healing. Lastly, we address emerging challenges and prospects in angiogenesis-enhancing DDS for facilitating DW healing, aiming to offer a comprehensive understanding of this critical healthcare issue and potential solutions.

Integration of miRNA in exosomes and single-cell RNA-seq profiles in endemic osteoarthritis, Kashin-Beck disease.

Kashin-Beck disease (KBD) is an endemic, chronic degenerative joint disease in China. Exosomes miRNAs, as signaling molecules in intercellular communication, can transfer specific biological martials into target cell to regulate their function and might participate in the pathogenesis of KBD. We isolated serum and chondrocytes-derived exosomes, miRNA sequencing revealed exosomes miRNA profiles and differentially expressed miRNAs (DE-miRNAs) were identified. The target genes were predicted of known and novel DE-miRNAs with TargetScan 5.0 and miRanda 3.3a database. Single-cell RNA sequencing (scRNA-seq) was performed to identify chondrocyte clusters and their gene signatures in KBD. And we performed comparative analysis between the serum and chondrocytes-derived exosomes DE-miRNA target genes and differentially expressed genes of each cell clusters. A total of 20 DE-miRNAs were identified in serum-derived exosomes. In the miRNA expression of chondrocytes-derived exosomes, 53 DE-miRNAs were identified. 16,063 predicted targets were identified as the target genes in the serum-derived exosomes, 57,316 predicted targets were identified as the target genes in the chondrocytes-derived exosomes. Seven clusters were labeled by cell type according to the expression of previously described markers. Three hundred fifteen common genes were found among serum/chondrocytes-derived exosomes DE-miRNA target genes and DEGs identified by scRNA-seq analysis. We firstly integratly analyzed the serum and chondrocytes exosomes miRNA with single-cell RNA sequencing (scRNA-seq) data of KBD chondrocyte, the results showed that DE-miRNAs in exosomes might play a potential role in regulating genes expression in different KBD chondrocytes clusters by exosomes mediating cell-cell communications functions, which could improve the new diagnosis and treatment methods for KBD.

Comparative Analysis of Gut Microbiota from Rats Induced by Se Deficiency and T-2 Toxin.

The aim of this study was to analyze the differences in gut microbiota between selenium deficiency and T-2 toxin intervention rats. Knee joint and fecal samples of rats were collected. The pathological characteristics of knee cartilage were observed by safranin O/fast green staining. DNA was extracted from fecal samples for PCR amplification, and 16S rDNA sequencing was performed to compare the gut microbiota of rats. At the phylum level, Firmicutes (81.39% vs. 77.06%) and Bacteroidetes (11.11% vs. 14.85%) were dominant in the Se-deficient (SD) group and T-2 exposure (T-2) groups. At the genus level, the relative abundance of Ruminococcus_1 (12.62%) and Ruminococcaceae_UCG-005 (10.31%) in the SD group were higher. In the T-2 group, the relative abundance of Lactobacillus (11.71%) and Ruminococcaceae_UCG-005 (9.26%) were higher. At the species level, the high-quality bacteria in the SD group was Ruminococcus_1_unclassified, and Ruminococcaceae_UCG-005_unclassified in the T-2 group. Lactobacillus_sp__L_YJ and Lactobacillus_crispatus were the most significant biomarkers in the T-2 group. This study analyzed the different compositions of gut microbiota in rats induced by selenium deficiency and T-2 toxin, and revealed the changes in gut microbiota, so as to provide a certain basis for promoting the study of the pathogenesis of Kashin-Beck disease (KBD).

Bioprinting-Enabled Biomaterials: A Cutting-Edge Strategy for Future Osteoarthritis Therapy.

Bioprinting is an advanced technology that allows for the precise placement of cells and biomaterials in a controlled manner, making significant contributions in regenerative medicine. Notably, bioprinting-enabled biomaterials have found extensive application as drug delivery systems (DDS) in the treatment of osteoarthritis (OA). Despite the widespread utilization of these biomaterials, there has been limited comprehensive research summarizing the recent advances in this area. Therefore, this review aims to explore the noteworthy developments and challenges associated with utilizing bioprinting-enabled biomaterials as effective DDS for the treatment of OA. To begin, we provide an overview of the complex pathophysiology of OA, highlighting the shortcomings of current treatment modalities. Following this, we conduct a detailed examination of various bioprinting technologies and discuss the wide range of biomaterials employed in DDS applications for OA therapy. Finally, by placing emphasis on their transformative potential, we discuss the incorporation of crucial cellular components such as chondrocytes and mesenchymal stem cells into bioprinted constructs, which play a pivotal role in promoting tissue regeneration and repair.

[Effectiveness analysis of percutaneous parallel screw fixation via posterolateral "safe zone" for Hawkins type â - â ¢ talar neck fractures].

Objective: To explore the effectiveness of the percutaneous parallel screw fixation via the posterolateral "safe zone" for Hawkins type Ⅰ-Ⅲ talar neck fractures. Methods: A retrospective analysis was conducted on the clinical data from 35 patients who met the selection criteria of talar neck fractures between January 2019 and June 2021. According to the surgical method, they were divided into a study group (14 cases, using percutaneous posterolateral "safe zone" parallel screw fixation) and a control group (21 cases, using traditional open reduction and anterior cross screw internal fixation). There was no significant difference in gender, age, affected side, Hawkins classification, and time from injury to operation between the two groups ( P>0.05). The operation time, bone healing time, complications, and Hawkins sign were recorded, and the improvement of pain and ankle-foot function were evaluated by visual analogue scale (VAS) score and American Orthopaedic Foot and Ankle Society (AOFAS) ankle and hindfoot score at last follow-up. The overall quality of life was assessed by the short form of 12-item health survey (SF-12), which was divided into physical and psychological scores; and the satisfaction of patients was evaluated by the 5-point Likert scale. Results: The operation time in the study group was significantly shorter than that in the control group ( P<0.05). All patients werefollowed up 13-35 months, with an average of 20.6 months; there was no significant difference in the follow-up time between the two groups ( P>0.05). The time of bone healing in the study group was shorter than that in the control group, and the positive rate of Hawkins sign (83.33%) was higher than that in the control group (33.33%), and the differences were significant ( P<0.05). In the control group, there were 2 cases of incision delayed healing, 7 cases of avascular necrosis of bone, 3 cases of joint degeneration, 1 case of bone nonunion, and 3 cases of internal fixation irritation; while in the study group, there were only 2 cases of joint degeneration, and there was a significant difference in the incidence of complications between the two groups ( P<0.05). At last follow-up, there was no significant difference in VAS score between the two groups ( P>0.05), but the SF-12 physical and psychological scores, AOFAS ankle and hindfoot scores, and patients' satisfaction in the study group were significantly better than those in the control group ( P<0.05). Conclusion: The treatment of Hawkins type Ⅰ-Ⅲ talar neck fractures with percutaneous parallel screw fixation via the posterolateral "safe zone" can achieve better effectiveness than traditional open surgery, with the advantages of less trauma, fewer complications, faster recovery, and higher patient satisfaction.

[Progress in clinical diagnosis and treatment of diabetic Charcot neuroarthropathy of foot and ankle].

Objective: To summarize the progress of clinical diagnosis and treatment of diabetic Charcot neuroarthropathy (CNO) of foot and ankle to provide reference for clinical treatment. Methods: The research literature on diabetic CNO of foot and ankle at home and abroad was widely reviewed, and the stages and classification criteria of CNO were summarized, and the treatment methods at different stages of the disease course were summarized. Results: CNO is a rapidly destructive disease of bone and joint caused by peripheral neuropathy, which leads to the formation of local deformities and stress ulcers due to bone and joint destruction and protective sensory loss, which eventually leads to disability and even life-threatening. At present, the modified Eichenholtz stage is a commonly used staging criteria for CNO of foot and ankle, which is divided into 4 stages by clinical and imaging manifestations. The classification mainly adopts the modified Brodsky classification, which is divided into 6 types according to the anatomical structure. The treatment of diabetic CNO of foot and ankle needs to be considered in combination with disease stage, blood glucose, comorbidities, local soft tissue conditions, degree of bone and joint destruction, and whether ulcers and infections are present. Conservative treatment is mainly used in the active phase and surgery in the stable phase. Conclusion: The formulation of individualized and stepped treatment regimens can help improve the effectiveness of diabetic CNO of foot and ankle. However, there is still a lack of definitive clinical evidence to guide the treatment of active and stable phases, and further research is needed.

Musculoskeletal Ultrasound for the Diagnosis of Plantar Fasciitis: An Accuracy and Diagnostic Yield Study.

Objective: To evaluate the accuracy of musculoskeletal ultrasound measurement of plantar fascia thickness and shear wave elastography (SWE) calculation of Young's modulus in the diagnosis of plantar fasciitis (PFis), and to explore whether it will have any impact on clinical decision-making, rather than just using established diagnostic methods of clinical symptoms and signs. Methods: A diagnostic single-center study was conducted in 60 patients with PFis and 64 patients with other types of heel pain. The sensitivity and specificity of musculoskeletal ultrasound in the diagnosis of PFis were calculated according to the diagnostic criteria for PFis recommended by the Clinical Practice Guide for PFis of the American Physical Therapy Association (APTA) Orthopaedic Branch. The analysis of the receiver operating characteristic curve of the subjects was used to study the accuracy of the diagnosis of PFis by two indicators alone and two indicators jointly. Results: The thickness of plantar fascia measured by musculoskeletal ultrasound and the area under the curve (AUCs) calculated by shear wave elastography for diagnosing PFis were 0.925 and 0.917, respectively, and the optimal cutoff values were 3.15 mm (sensitivity: 100.0%, specificity: 81.3%) and 63.24 kPa (sensitivity: 78.3%, specificity: 92.2%), respectively. The area under the curve (AUCs) for the combined diagnosis of the two is 0.973 (sensitivity: 93.3%, specificity: 93.8%). Conclusion: The thickness of plantar fascia measured by musculoskeletal ultrasound and Young's modulus calculated by SWE have high accuracy in diagnosing PFis, and the combined diagnosis of the two can improve the diagnostic accuracy of patients with PFis.

Therapeutics of osteoarthritis and pharmacological mechanisms: A focus on RANK/RANKL signaling.

Osteoarthritis (OA) is a chronic degenerative disease afflicting millions globally. Despite the development of numerous pharmacological treatments for OA, a substantial unmet need for effective therapies persists. The RANK/RANKL signaling pathway has emerged as a promising therapeutic target for OA, owing to its pivotal role in regulating osteoclast differentiation and activity. In this comprehensive review, we aim to elucidate the relevant mechanisms of OA mediated by RANK/RANKL signaling, including bone remodeling, inflammation, cartilage degradation, osteophyte formation, and pain sensitization. Furthermore, we discuss and summarize the cutting-edge strategies targeting RANK/RANKL signaling for OA therapy, encompassing approaches such as gene-based interventions and biomaterials-aided pharmacotherapy. In addition, we highlight the prevailing challenges associated with pharmacological OA treatments and explore potential future directions, approached through a clinical-translational lens.

Integrative analysis of miRNA in cartilage-derived extracellular vesicles and single-cell RNA-seq profiles in knee osteoarthritis.

Extracellular vesicular miRNAs (EV-miRNAs) play essential roles as intercellular communication molecules in knee Osteoarthritis (OA). We isolated cartilage-derived extracellular vesicles (EVs), to perform miRNA sequencing, which revealed EV-miRNA profiles and identified differentially expressed miRNAs (DE-miRNAs) between cartilage injury and cartilage non-injury groups. The target genes of known and novel DE-miRNAs were predicted with multiMiR package in 14 miRNA-target interaction databases. Meanwhile, single-cell RNA sequencing (scRNA-seq) was performed to identify chondrocyte clusters and their gene signatures in knee OA. Then we performed comparative analysis between target genes of the cartilage-derived EV-DE-miRNAs target genes and cluster-specific maker genes of characteristic chondrocyte clusters. Finally, the functional analysis of the cartilage-derived EVs DE-miRNA target genes and cluster-specific marker genes of each cell population were performed. The EV-miRNA profile analysis identified 13 DE-miRNAs and 7638 target genes. ScRNA-seq labelled seven clusters by cell type according to the expression of multiple characteristic markers. The results identified 735, 184, 303 and 879 common genes between EV-DE-miRNA target genes and cluster-specific marker genes in regulatory chondrocytes (RegCs), fibrocartilage chondrocytes (FC), prehypertrophic chondrocytes (PreHTCs) and mitochondrial chondrocytes (MTC), respectively. We firstly integrated the association between the cartilage-derived EV-DE-miRNA target genes and distinguished cluster-specific marker genes of each chondrocyte clusters. KEGG pathway analysis further identified that the DE-miRNAs target genes were significantly enriched in MAPK signaling pathway, Focal adhesion and FoxO signaling pathway. Our results provided some new insights into cartilage injury and knee OA pathogenesis which could improve the new diagnosis and treatment methods for OA.

Biomaterial-based scaffolds in promotion of cartilage regeneration: Recent advances and emerging applications.

Osteoarthritis (OA) poses a significant burden for countless individuals, inflicting relentless pain and impairing their quality of life. Although traditional treatments for OA focus on pain management and surgical interventions, they often fall short of addressing the underlying cause of the disease. Fortunately, emerging biomaterial-based scaffolds offer hope for OA therapy, providing immense promise for cartilage regeneration in OA. These innovative scaffolds are ingeniously designed to provide support and mimic the intricate structure of the natural extracellular matrix, thus stimulating the regeneration of damaged cartilage. In this comprehensive review, we summarize and discuss current landscape of biomaterial-based scaffolds for cartilage regeneration in OA. Furthermore, we delve into the diverse range of biomaterials employed in their construction and explore the cutting-edge techniques utilized in their fabrication. By examining both preclinical and clinical studies, we aim to illuminate the remarkable versatility and untapped potential of biomaterial-based scaffolds in the context of OA. Thetranslational potential of this article: By thoroughly examining the current state of research and clinical studies, this review provides valuable insights that bridge the gap between scientific knowledge and practical application. This knowledge is crucial for clinicians and researchers who strive to develop innovative treatments that go beyond symptom management and directly target the underlying cause of OA. Through the comprehensive analysis and multidisciplinary approach, the review paves the way for the translation of scientific knowledge into practical applications, ultimately improving the lives of individuals suffering from OA and shaping the future of orthopedic medicine.

Modified hindfoot alignment radiological evaluation and application in the assessment of flatfoot.

BACKGROUND: Alignment is indispensable for the foot and ankle function, especially in the hindfoot alignment. In the preoperative planning of patients with varus or valgus deformity, the precise measurement of the hindfoot alignment is important. A new method of photographing and measuring hindfoot alignment based on X-ray was proposed in this study, and it was applied in the assessment of flatfoot. METHODS: This study included 28 patients (40 feet) with flatfeet and 20 volunteers (40 feet) from January to December 2018. The hindfoot alignment shooting stand independently designed by our department was used to take hindfoot alignment X-rays at 10 degree, 15 degree, 20 degree, 25 degree, and 30 degree. We measured the modified tibio-hindfoot angle (THA) at the standard hindfoot aligment position (shooting at 20 degree) and evaluated consistency with the van Dijk method and the modified van Dijk method. In addition, we observed the visibility of the tibiotalar joint space from all imaging data at five projection angles and evaluated the consistency of the modified THA method at different projection angles. The angle of hindfoot valgus of flatfoot patients was measured using the modified THA method. RESULTS: The mean THA in the standard hindfoot aligment view in normal people was significantly different among the three evaluation methods (P < .001). The results from the modified THA method were significantly larger than those from the Van Dijk method (P < .001) and modified Van Dijk method (P < .001). There was no significant difference between the results of the modified THA method and the weightbearing CT (P = .605), and the intra- and intergroup consistency were the highest in the modified THA group. The tibiotalar space in the normal group was visible in all cases at 10 degree, 15 degree, and 20 degree; visible in some cases at 25 degree; and not visible in all cases at 30 degree. In the flatfoot group, the tibiotalar space was visible in all cases at 10 degree, visible in some cases at 15 degree and 20 degree, and not visible in all cases at 25 degree and 30 degree. In the normal group, the modified THA was 4.84 ± 1.81 degree at 10 degree, 4.96 ± 1.77 degree at 15 degree, and 4.94 ± 2.04 degree at 20 degree. No significant differences were found among the three groups (P = .616). In the flatfoot group, the modified THA of 18 feet, which was visible at 10 degree, 15 degree and 20 degree, was 13.58 ± 3.57 degree at 10 degree, 13.62 ± 3.83 degree at 15 degree and 13.38 ± 4.06 degree at 20 degree. There were no significant differences among the three groups (P = .425). CONCLUSIONS: The modified THA evaluation method is simple to use and has high inter- and intragroup consistency. It can be used to evaluate hindfoot alignment. For patients with flatfeet, the 10 degree position view and modified THA measurement can be used to evaluate hindfoot valgus.

Changes in the subtalar joint alignment after supramalleolar osteotomy for varus ankle arthritis.

BACKGROUND: The subtalar joint may compensate for tibio-talar deformity, but what would happen to the joint after the deformity was corrected is not well known. Supramalleolar osteotomy (SMOT) is an effective procedure for the treatment of varus deformity of ankle arthritis. The objective of this study was to investigate the subtalar joint alignment pre and postoperatively following SMOT, and the factors which influenced the alignment of the subtalar joint. METHODS: Thirty-one patients with varus ankle arthritis (Takakura stage 2, 3a and 3b) who were treated using SMOT were retrospectively reviewed. The subtalar and ankle joint alignment was measured on weightbearing radiograph and weightbearing computerized tomography (WBCT). RESULTS: The foot and ankle offset (FAO), tibial articular surface angle (TAS), tibio-talar surface angle (TTS), and subtalar vertical angle (SVA) were significantly corrected (P＜0.05). The subtalar inclination angle (SIA) decreased in 19 patients and increased in the other 12 cases after the SMOT (P＜0.001). The shift of subtalar joint (ΔSIA) showed an inverse correlation with the preoperative FAO (P＜0.001, r = -0.621). CONCLUSIONS: The shift of subtalar joint after SMOT could maintain the neutral position of the hindfoot and showed a negative correlation with the preoperative FAO. The ΔSIA was greater in the severer preoperative hindfoot deformity. LEVEL OF EVIDENCE: Level IV, case series.

Harnessing exosomes as cutting-edge drug delivery systems for revolutionary osteoarthritis therapy.

Exosomes, remarkable extracellular vesicles, have emerged as an advanced frontier in intercellular communication. This remarkable capacity positions them as promising contenders in drug delivery systems (DDSs) for osteoarthritis (OA) therapy, capitalizing on their inherent biocompatibility, stability, and minimal immunogenicity. In this comprehensive review, we summarize the emerging developments surrounding exosome-based DDSs for OA therapy. Focusing on exosome origins, we meticulously explore the diverse sources contributing to their production, including invaluable stem cells, immune cells, and an array of other cell types. In addition, we unravel the underlying mechanisms of action that govern these exosome-borne therapeutics, illuminating the intricate interplay between exosomes and recipient cells. In summary, this review highlights the present challenges that permeate exosome-based DDSs for OA therapy. Through an in-depth exploration of the intricacies within this emerging field, this review aims to shed light on the future direction of exosome-based DDSs in OA. It serves as a bridge for fostering collaboration and collective efforts in reshaping the treatment landscape of OA.

[Effectiveness and risk factors of supramalleolar osteotomy in treatment of varus-type ankle arthritis].

Objective: To assess the effectiveness of supramalleolar osteotomy (SMOT) as a therapeutic intervention for varus-type ankle arthritis, while also examining the associated risk factors that may contribute to treatment failure. Methods: The clinical data of 82 patients (89 feet) diagnosed with varus-type ankle arthritis and treated with SMOT between January 2016 and December 2020 were retrospectively analyzed. The patient cohort consisted of 34 males with 38 feet and 48 females with 51 feet, with the mean age of 54.3 years (range, 43-72 years). The average body mass index was 24.43 kg/m 2 (range, 20.43-30.15 kg/m 2). The preoperative tibial anterior surface angle (TAS) ranged from 77.6° to 88.4°, with a mean of 84.4°. The modified Takakura stage was used to classify the severity of the condition, with 9 feet in stage Ⅱ, 41 feet in stage Ⅲa, and 39 feet in stage Ⅲb. Clinical functional assessment was conducted using the Maryland sore, visual analogue scale (VAS) score, and psychological and physical scores in Health Survey 12-item Short From (SF-12). Radiology evaluations include TAS, talar tilt (TT), tibiocrural angle (TC), tibial medial malleolars (TMM), tibiocrural distance (TCD), tibial lateral surface angle (TLS), and hindfoot alignment angle (HAA). The results of clinical failure, functional failure, and radiology failure were statistically analyzed, and the related risk factors were analyzed. Results: The operation time ranged from 45 to 88 minutes, with an average of 62.2 minutes. No complication such as fractures and neurovascular injuries was found during operation. There were 7 feet of poor healing of the medial incision; 9 pin tract infections occurred in 6 feet using external fixator; there were 20 cases of allograft and 3 cases of autograft with radiographic bone resorption. Except for 1 foot of severe infection treated with bone cement, the remaining 88 feet were primary healing, and the healing area was more than 80%. All patients were followed up 24-82 months, with an average of 50.2 months. Maryland score, VAS score, SF-12 psychological and physiological scores, and TAS, TC, TLS, TCD, TT, TMM, HAA, and Takakura stage were significantly improved at last follow-up ( P<0.05). Postoperative clinical failure occurred in 13 feet, functional failure in 15 feet, and radiology failure in 23 feet. Univariate analysis showed that obesity, TT>10°, and Takakura stage Ⅲb were risk factors for clinical failure, HAA≥15° and Takakura stage Ⅲb were risk factors for functional failure, and TT>10° was risk factor for radiographic failure ( P<0.05). Further logistic regression analysis showed that TT>10°, HAA≥15°, and TT>10° were risk factors for clinical failure, functional failure, and radiographic failure, respectively ( P<0.05). Conclusion: SMOT is effective in the mid- and long-term in the treatment of varus-type ankle arthritis, but it should be used with caution in patients with obesity, severe hindfoot varus, severe talus tilt, and preoperative Takakura stage Ⅲb.

Therapeutics of Charcot neuroarthropathy and pharmacological mechanisms: A bone metabolism perspective.

Charcot neuroarthropathy (CN) is a chronic, destructive, and painless damage of the skeletal system that affects the life quality of patients. CN, with an unclear mechanism, is characterized with invasive destruction of bones and a serious abnormality of bone metabolism. Unfortunately, development of an effective prevention and treatment strategy for CN is still a great challenge. Of note, recent studies providing an insight into the molecular mechanisms of bone metabolism and homeostasis have propelled development of novel CN therapeutic strategies. Therefore, this review aims to shed light on the pathogenesis, diagnosis, and treatment of CN. In particular, we highlight the eminent role of the osteoprotegerin (OPG)-receptor activator of nuclear factor-κB (RANK)-RANK ligand (RANKL) system in the development of CN. Furthermore, we summarize and discuss the diagnostic biomarkers of CN as well as the potential pharmacological mechanisms of current treatment regimens from the perspective of bone metabolism. We believe that this review will enhance the current state of knowledge on the diagnosis, prevention, and therapeutic efficacy of CN.

Cartilage Damage Pathological Characteristics of Diabetic Neuropathic Osteoarthropathy.

Background: Diabetic neuropathic osteoarthropathy (DNOAP) is a rare and easily missed complication for diabetes that leads to increased morbidity and mortality. DNOAP is characterized by progressive destruction of bone and joint, but its pathogenesis remains elusive. We herein aimed to investigate the pathological features and pathogenesis of the cartilages damage in DNOAP patients. Methods: The articular cartilages of eight patients with DNOAP and eight normal controls were included. Masson staining and safranine O/fixed green staining (S-O) were used to observe the histopathological characteristics of cartilage. The ultrastructure and morphology of chondrocytes were detected by electron microscopy and toluidine blue staining. Chondrocytes were isolated from DNOAP group and control group. The expression of receptor activator of nuclear factor kappaB ligand (RANKL), osteoprotegerin (OPG), interleukin-1 beta (IL-1ß), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and Aggrecan protein was evaluated by western blot. Reactive oxygen species (ROS) levels were measured using a 2',7'-dichlorofluorescin diacetate (DCFH-DA) probe. The percentage of apoptotic cells was determined by flow cytometry (FCM). The chondrocytes were cultured with different glucose concentrations to observe the expression of RANKL and OPG. Results: Compared with the control group, the DNOAP group showed fewer chondrocytes, subchondral bone hyperplasia, and structural disorder, and a large number of osteoclasts formed in the subchondral bone area. Moreover, mitochondrial and endoplasmic reticulum swellings were observed in the DNOAP chondrocytes. The chromatin was partially broken and concentrated at the edge of nuclear membrane. The ROS fluorescence intensity of chondrocyte in DNOAP group was higher than that in normal control group (28.1 ± 2.3 vs. 11.9 ± 0.7; P < 0.05). The expression of RANKL, TNF-α, IL-1ß, and IL-6 protein in DNOAP group was higher than that in normal control group, whereas OPG and Aggrecan protein were lower than that in normal control group (both P < 0.05). FCM showed that the apoptotic rate of chondrocyte in DNOAP group was higher than that in normal control group (P < 0.05). The RANKL/OPG ratio showed significant upward trend when the concentration of glucose was over than 15 mM. Conclusions: DNOAP patients tend to have severe destruction of articular cartilage and collapse of organelle structure including mitochondrion and endoplasm reticulum. Indicators of bone metabolism (RANKL and OPG) and inflammatory cytokines (IL-1ß, IL-6, and TNF-α) play an important role in promoting the pathogenesis of DNOAP. The glucose concentration higher than 15 mM made the RANKL/OPG ratio change rapidly.

Altered gut microbiome profile in patients with knee osteoarthritis.

Introduction: Osteoarthritis (OA) is a kind of chronic, degenerative disorder with unknown causes. In this study, we aimed to improve our understanding of the gut microbiota profile in patients with knee OA. Methods: 16S rDNA gene sequencing was performed to detect the gut microbiota in fecal samples collected from the patients with OA (n = 32) and normal control (NC, n = 57). Then the metagenomic sequencing was used to identify the genes or functions linked with gut microbial changes at the species level in the fecal samples from patients with OA and NC groups. Results: The Proteobacteria was identified as dominant bacteria in OA group. We identified 81 genera resulted significantly different in abundance between OA and NC. The abundance of Agathobacter, Ruminococcus, Roseburia, Subdoligranulum, and Lactobacillus showed significant decrease in the OA compared to the NC. The abundance of genera Prevotella_7, Clostridium, Flavonifractor and Klebsiella were increasing in the OA group, and the families Lactobacillaceae, Christensenellaceae, Clostridiaceae_1 and Acidaminococcaceae were increasing in the NC. The metagenomic sequencing showed that the abundance of Bacteroides stercoris, Bacteroides vulgatus and Bacteroides uniformis at the species level were significantly decreasing in the OA, and the abundance of Escherichia coli, Klebsiella pneumoniae, Shigella flexneri and Streptococcus salivarius were significantly increased in OA. Discussion: The results of our study interpret a comprehensive profile of the gut microbiota in patients with knee OA and offer the evidence that the cartilage-gut-microbiome axis could play a crucial role in underlying the mechanisms and pathogenesis of OA.